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Digestion of Human Milk Oligosaccharides by Bifidobacterium breve in the Premature Infant

Underwood, Mark A.*; Davis, Jasmine C.C.; Kalanetra, Karen M.; Gehlot, Sanjay§; Patole, Sanjay§; Tancredi, Daniel J.*; Mills, David A.; Lebrilla, Carlito B.; Simmer, Karen§

Journal of Pediatric Gastroenterology and Nutrition: October 2017 - Volume 65 - Issue 4 - p 449–455
doi: 10.1097/MPG.0000000000001590
Original Articles: Nutrition

Objective: The aim of this study was to measure consumption and absorption of human milk oligosaccharides (HMOs) in a cohort of premature infants treated with probiotic Bifidobacterium breve.

Methods: Twenty-nine premature infants (median gestational age 28 weeks, range 23–32 weeks) cared for in the neonatal intensive care unit of the King Edward and Princess Margaret Hospital in Perth, Australia, were treated with B breve at a dose of 1.66 billion organisms per day. Samples of feces, urine, and milk were obtained at initiation of the probiotic and again 3 weeks later. 16S ribosomal RNA from the feces was analyzed by next-generation sequencing. Quantitation of HMO content of the milk, urine, and feces was performed using nano-high-performance liquid chromatography-chip/time-of-flight mass spectrometry.

Results: There was heterogeneity in colonization with bifidobacteria. “Responders” received milk with higher percentages of fucosylated HMOs and had higher percentages of bifidobacteria and lower percentages of Enterobacteriaceae in their feces than “nonresponders.” Several individual HMOs in the milk were associated with changes in fecal bifidobacteria over time. Changes over time in milk, fecal, and urine HMOs suggested heterogeneity among HMO structures in consumption by microbes in the gut lumen and absorption from the intestine.

Conclusions: Colonization of the premature infant intestinal tract with probiotic B breve is influenced by prebiotic HMOs. B breve is a selective consumer of HMOs in the premature infant.

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*Department of Pediatrics, University of California Davis, Sacramento, CA

Department of Chemistry, University of California Davis, Davis, CA

Department of Food Science and Technology, University of California Davis, Davis, CA

§Centre for Neonatal Research and Education, University of Western Australia, Perth, Australia

Address correspondence and reprint requests to Mark A. Underwood, MD, UC Davis School of Medicine, Ticon 2 Suite 253, 2516 Stockton Blvd, Sacramento, CA 95817 (e-mail:

Received 23 November, 2016

Accepted 3 March, 2017

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Drs Mills and Lebrilla are cofounders of Evolve Biosystems, a company focused on diet-based manipulation of the gut microbiota. This work was funded in part by National Institutes of Health Awards AT007079, HD065122 and AT008759, and the Peter J. Shields Endowed Chair in Dairy Food Science.

The authors report no conflicts of interest.

© 2017 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,